On Jul 5, 6:32=A0pm, jay <jaym1...@[EMAIL PROTECTED]
> wrote:
> > direct link between IBD and Dioxins? didn't find one, but ...
>
> Below abstract indicate that TCDD can incease TNF:
TCDD, an omnipresent, persistent, potent, slow-acting toxin alters a
diverse number of biological processes. One of them is to increase
inflammation to common & uncommon type/level of bacterial, viral and
dietary antigens.
The effects of TCDD on TNF production by peritoneal cells.
Recent studies in mice have demonstrated that TNF plays a critical
role in mediating the TCDD-induced enhanced inflammatory response to
intraperitoneal (i.p.) sheep red blood cells. The current studies were
designed to evaluate the effects of TCDD on TNF production by ex-vivo
peritoneal cells and a peritoneal macrophage cell line (IC-21)
stimulated with LPS. In sup****t of the hypothesis that TCDD can act
directly on the peritoneal macrophage to increase TNF production,
following pretreatment with TCDD, both ex-vivo peritoneal cells and
IC-21 cells produced increased levels of bioactive TNF when stimulated
with LPS. Flow cytometric analyses of IC-21 cells indicate that TCDD
exposure increases intracellular production and secretion of TNF but
does not alter levels of membrane associated TNF. PMID: 9067482
Cytokines (IL-1beta and TNFalpha) in relation to biochemical and
immunological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in
rats.
Previous studies in different strains of rats and mice have shown that
the inhibition of gluconeogenesis as a result of reduced liver
phosphoenolpyruvate carboxykinase (PEPCK) activity together with
appetite suppression play critical roles in the acute toxicity of
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Recent immunological
studies in rats demonstrated that exposure to low doses of TCDD
resulted in an early and enhanced IgG response to immunization with
sheep red blood cells (SRBC) and an enhanced delayed-type
hypersensitivity (DTH) reaction as well as a positive popliteal lymph
node (PLN) response. However, high doses of TCDD suppressed the DTH
reaction. This study aimed at examining the involvement of cytokines
(IL-1 and TNF) in mediating the above effects. Liver samples from a
previous dose-response study on DTH reaction were investigated, in
which rats were treated with TCDD (1, 3, 10, 30 and 90 microg/kg) and
immunized with an antigen. mRNA levels of IL-1beta were elevated
begining at the 1 microg/kg (non-lethal) dosage group with a maximum
increase of about 5-fold above controls in the 90 microg/kg (lethal)
dosage group. mRNA levels of TNFalpha were also significantly elevated
begining at the 30 microg/kg dosage group. These results suggest that
at low doses of TCDD, increased IL-1beta could be responsible for
immune function stimulation, whereas at high doses of TCDD, greatly
elevated TNFalpha and IL-1beta levles may exacerbate or mediate acute
toxicity including immune suppression and related biochemical effects.
A time course study (60 microg TCDD/kg without immunization) revealed
that liver mRNA levels of TNFalpha were significantly elevated
starting 24 h, and reaching a maximum 48 h after dosing with TCDD.
This change was accompanied by a transient increase of mRNA levels of
IL-1beta at day 4 after TCDD dosage. Thus, these data demonstrated
that TCDD alone (without immunization) can cause transient increases
of mRNA levels of TNFalpha and IL-1beta in liver. Results from these
experiments suggest that TCDD-induced cytokine changes may play
im****tant roles in various effects of TCDD. PMID: 9020502
Influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on TNF-alpha
levels in the skin of congenic haired and hairless mice.
It has been proposed that TNF-alpha mediates TCDD-induced toxicity.
TCDD induces a chloracne-like response in the skin of hairless HRS/J
mice but not in congenic haired animals. Using an ELISA, we measured
TNF-alpha levels in the skin of TCDD-treated haired and hairless HRS/J
mice to test the hypothesis that TNF-alpha mediates the cutaneous
toxicity of TCDD. TNF-alpha levels in the skin of haired mice were at
or below minimal detectable levels and were unchanged by TCDD
exposure. In contrast, TNF-alpha levels were significantly higher in
the skin of hairless mice after TCDD exposure. The bulk of the induced
TNF-alpha was present in the dermis, although detectable amounts were
present in the epidermis. To determine if murine skin cells were
producing TNF-alpha in direct response to TCDD, cultures of neonatal
epidermal keratinocytes and dermal fibroblasts were treated with
varying biologically active doses of TCDD or vehicle (DMSO) or with
lipopolysaccharide (LPS) as a positive control. Within 24 hr of
exposure to LPS, TNF-alpha levels were increased in the culture media
of all cells tested. In contrast, TCDD treatment (10(-11) M to 10(-7)
M) failed to induce detectable TNF-alpha release from either
fibroblasts or keratinocytes over a comparable time frame or when
measured for up to 6 days following exposure. The failure of TCDD to
stimulate TNF-alpha production by keratinocytes or fibroblasts
suggests that the rise in dermal TNF-alpha levels seen in vivo is
unlikely to be a primary component of the mechanism of toxicity. We
suggest that the source of the dermal TNF-alpha in TCDD-treated
hairless mouse skin is probably component cells of the inflammatory
response. PMID: 7974484
Tumor necrosis factor involvement in 2,3,7,8-tetrachlorodibenzo-p-
dioxin-mediated endotoxin hypersensitivity in C57BL/6J mice congenic
at the Ah locus.
An experimental model of endotoxin-induced release of tumor necrosis
factor-alpha (TNF) into the serum of C57BL/6J mice congenic at the Ah
locus was used to investigate the effects of 2,3,7,8-
Tetrachlorodibenzo-p-dioxin (TCDD) on TNF production. TCDD exposure of
Ah-responsive mice (Ahbb) resulted in a dose-dependent increase in the
concentration of TNF in the serum of endotoxin-exposed mice, with a
significant increase observed at a dose of 10 micrograms/kg TCDD. At a
dose of 500 micrograms/kg TCDD, Ahbb mice demonstrated a 46-fold
increase in serum TNF levels compared to control. In contrast,
congenic Ah-receptor deficient mice (Ahdd) did not show a significant
increase in serum TNF levels until exposed to 150 micrograms/kg TCDD,
and the maximum response was an 8-fold increase over control. These
data suggest that increased TNF production may be responsible for
endotoxin hypersensitivity in TCDD-treated mice and that the Ah locus
mediates this response. PMID: 1660630
Hmm, seems DOW, Monsanto, and the gov has known the effects of TCDD
for decades. Not only is there no profit in removing persistent
pollutants from the environment, it is very expensive, so industry is
quite resistant. Actually US EPA/FDA have been working to reduce TCDD
levels (supposedly 2.2 pg/kg in 2005 per one source) but it is still
higher than acceptable, thus it wont publically announce a safe level.
Mean while, World Health Org (WHO) recommends less than 1 pg/kg in the
future. There is profit in selling treatments, but not in finding the
root cause as this would make a lot of people look bad. People will
have to be proactive in protecting their health because trackdown a
problems 5 to 10 years after consuming dioxin contaminated fish is
difficult.
|
